Evaluation of the mechanistic basis for the antibacterial activity of ursolic acid against Staphylococcus aureus.

The antibiotics are generally regarded as the first choice approach to treat dairy mastitis, targeting the public health problems associated with the food safety and the emergence of antibioticresistant bacteria. The objective of the study was to evaluate the antibacterial efficacy of ursolic acid (UA) when used to treat Staphylococcus aureus and other isolates associated with bovine mastitis and to clarify the mechanistic basis for these effects. The bacteriostatic properties of UA extracted from Rosmarinus officinalis L. at four different purity levels were assessed by calculating minimum inhibitory concentration (MIC) values, while the synergistic effects of combining 98% UA with antibiotics were evaluated by measuring the fractional inhibitory concentration index (FICI). Changes in biofilm formation and the growth curves of the clinical isolates were assessed to clarify the bacteriostatic effect of UA. Furthermore, the cell wall integrity, protein synthesis, and reactive oxygen species (ROS) production were assessed to determine the antibacterial mechanism of UA treatment. Ultimately, UA was revealed to exhibit robust activity against Gram-positive bacteria including S. aureus (ATCC 25923), Streptococcus dysgalactiae (ATCC27957), Streptococcus agalactiae (ATCC13813), Enterococcus faecalis (ATCC29212), and Streptococcus mutans (ATCC25175). However, it did not affect Escherichia coli (ATCC 25922). The MIC values of UA preparations that were 98, 50, 30, and 10% pure against S. aureus were 39, 312, 625, and 625 µg/mL, respectively, whereas the corresponding MIC for E. coli was >5,000 µg/mL. The minimum bactericidal concentrations of 98% UA when used to treat three clinical S. aureus isolates (S4, S5, and S6) were 78, 78, and 156 µg/mL, respectively. Levels of biofilm formation for clinical S. aureus isolates decreased with increasing 98% UA concentrations. Above the MIC dose, UA treatment resulted in the dissolution of bacterial cell walls and membranes, with cells becoming irregularly shaped and exhibiting markedly impaired intracellular protein synthesis. S. aureus treated with 98% UA was able to rapidly promote intracellular ROS biogenesis. Together, these data highlight the promising utility of UA as a compound that can be used together with other antibiotics for the treatment of infections caused by S. aureus.

Insight into the adsorption behaviors and bioaccessibility of three altered microplastics through three types of advanced oxidation processes.

Advanced oxidation processes (AOPs) can significantly alter the structural properties, environmental behaviors and human exposure level of microplastics in aquatic environments. Three typical microplastics (Polyethylene (PE), polypropylene (PP), and polystyrene (PS)) and three AOPs (Heat-K2S2O8 (PDS), UV-H2O2, UV-peracetic acid (PAA)) were adopted to simulate the process when microplastics exposed to the sewage disposal system. 2-Nitrofluorene (2-NFlu) adsorption experiments found the equilibrium time decreased to 24 hours and the capacity increased up to 610 µg g-1, which means the adsorption efficiency has been greatly improved. The fitting results indicate the adsorption mechanism shifted from the partition dominant on pristine microplastic to the physical adsorption (pore filling) dominant. The alteration of specific surface area (21 to 152 m2 g-1), pore volume (0.003 to 0.148 cm3 g-1) and the particle size (123 to 16 µm) of microplastics after AOPs are implying the improvement for pore filling. Besides, the investigation of bioaccessibility is more complex, AOPs alter microplastic with more oxygen-containing functional groups and lower hydrophobicity detected by XPS and water contact angle, those modifications have increased the sorption concentration, especially in the human intestinal tract. Therefore, this indicates the actual exposure of organic compounds loaded in microplastic may be higher than in the pristine microplastic. This study can help to assess the human health risk of microplastic pollution in actual environments.

Design strategies and recent development of bioactive modulators for glutamine transporters.

Glutamine transporters are integral to the metabolism of glutamine in both healthy tissues and cancerous cells, playing a pivotal role in maintaining amino acid balance, synthesizing biomolecules, and regulating redox equilibrium. Their critical functions in cellular metabolism make them promising targets for oncological therapies. Recent years have witnessed substantial progress in the field of glutamine transporters, marked by breakthroughs in understanding of their protein structures and the discovery of novel inhibitors, prodrugs, and radiotracers. This review provides a comprehensive update on the latest advancements in modulators targeting the glutamine transporter, with special attention given to LAT1 and ASCT2. It also discusses innovative approaches in drug design aimed at these transporters.

Preliminary Study on Total Component Analysis and In Vitro Antitumor Activity of Eucalyptus Leaf Residues.

Eucalyptus globulus is widely introduced and cultivated in Yunnan province. Its foliage is mainly used to extract eucalyptus oil, but the by-product eucalyptus residue has not been fully utilized. Based on the above reasons, in this study, we sought to explore the comprehensive utilization potential of eucalyptus resources. The total composition of eucalyptus residue was analyzed by ultra performance liquid chromatography-time-of-flight mass spectrometry (UPLC-Q/TOF MS), and the active components and nutrient components of eucalyptus leaf residue were determined by chemical methods and liquid phase techniques. Meanwhile, the antitumor activity of triterpenoids in eucalyptus leaves was evaluated by tetramethylazazole blue colorimetric assay (MTT). The results of qualitative analysis indicated that 55 compounds were identified from eucalyptus residue, including 28 phloroglucinols, 17 terpenoids, 3 flavonoids, 5 fatty acids, 1 amino acid and 2 polyphenols. Among them, the pentacyclic triterpenoids, in eucalyptus residue, were mainly oleanane type and urthane type. The results of quantitative determination indicated that the content of triterpenoid compounds was 2.84% in eucalyptus residue, which could be enhanced to 82% by silicone separation. The antitumor activity results showed that triterpenoid compounds have moderate inhibitory effects on human breast cancer cell MDA-MB-231, gastric adenocarcinoma cell SGC-7901 and cervical cancer cell Hela. The half maximal inhibitory concentration (IC50) was 50.67, 43.12 and 42.65 µg/mL, respectively. In this study, the triterpenoids from eucalyptus leaf residues were analyzed to reveal that the triterpenoids from eucalyptus leaf have antitumor effects and have potential to be developed as antitumor drugs.

Discovery of Novel Aminobutanoic Acid-Based ASCT2 Inhibitors for the Treatment of Non-Small-Cell Lung Cancer.

Alanine-serine-cysteine transporter 2 (ASCT2) is up-regulated in lung cancers, and inhibiting it could potentially lead to nutrient deprivation, making it a viable strategy for cancer treatment. In this study, we present a series of ASCT2 inhibitors based on aminobutanoic acids, which exhibit potent inhibitory activity. Two compounds, 20k and 25e, were identified as novel and potent ASCT2 inhibitors, with IC50 values at the micromolar level in both A549 and HEK293 cells, effectively blocking glutamine (Gln) uptake. Additionally, these compounds regulated amino acid metabolism, suppressed mTOR signaling, inhibited non-small-cell lung cancer (NSCLC) growth, and induced apoptosis. In vivo, experiments showed that 20k and 25e suppressed tumor growth in an A549 xenograft model, with tumor growth inhibition (TGI) values of 65 and 70% at 25 mg/kg, respectively, while V9302 only achieved a TGI value of 29%. Furthermore, both compounds demonstrated promising therapeutic potential in patient-derived organoids. Therefore, these ASCT2 inhibitors based on aminobutanoic acids are promising therapeutic agents for treating NSCLC by targeting cancer Gln metabolism.

Ursolic acid: biological functions and application in animal husbandry.

Ursolic acid (UA) is a plant-derived pentacyclic triterpenoid with 30 carbon atoms. UA has anti-inflammatory, antioxidative, antimicrobial, hepato-protective, anticancer, and other biological activities. Most studies on the biological functions of UA have been performed in mammalian cell (in vitro) and rodent (in vivo) models. UA is used in animal husbandry as an anti-inflammatory and antiviral agent, as well as for enhancing the integrity of the intestinal barrier. Although UA has been shown to have significant in vitro bacteriostatic effects, it is rarely used in animal nutrition. The use of UA as a substitute for oral antibiotics or as a novel feed additive in animal husbandry should be considered. This review summarizes the available data on the biological functions of UA and its applications in animal husbandry.

Sediment core records and impact factors of polycyclic aromatic hydrocarbons in Chinese lakes.

Lake sediment is a natural sink for polycyclic aromatic hydrocarbons (PAHs). PAH sedimentation characteristics and their impact factors of Chinese lakes have mainly been qualitative assessed. However, quantitative impacts of PAH sedimentation from different factors have not been well analyzed. To fill this gap, we screened PAH sedimentation records from the literature, for 51 lakes in China and other regions of the world, to identify historical concentration variation and the impact factors of PAHs in different regions, in lake sediment. The results show that PAH concentrations in the sediment core in the selected Chinese lakes (478 ± 812 ng/g dry weight (dw)) were significantly lower than those in North America (5518 ± 6572 ng/g dw) and Europe (3817 ± 4033 ng/g dw). From 1900 to 2015, most of the lakes in China showed an increasing trend of PAH sedimentation concentrations, with the lakes in Southeastern China showed a decreasing trend of PAH concentration in the period of 2001-2015, which was later than the peak times shown in Western countries (1941-1970). The 2-3-ring PAHs were the main components in the sediment core of Chinese lakes, but the proportion to the total PAHs decreased from 72% in 1900-1940 to 55% in 2001-2015. Generalized additive modeling (GAM) was adopted to simulate the associations between PAH sedimentation records and the impact factors. There are large regional variations of economic and industrial development in China. The impact factors of PAH accumulation in the lake sediments differ in different regions. However, population and the consumption of coal, pesticides, and fertilizer were identified to be the most important impact factors influencing PAH sedimentation. The Chinese government needs to strengthen control measures on pollutant discharge to reduce the anthropogenic impact of PAH sedimentation in lakes.

Inventory, source and health risk assessment of nitrated and parent PAHs in agricultural soils over a rural river in Southeast China.

Nitrated polycyclic aromatic hydrocarbons (NPAHs) have become a concerning topic because of their widespread occurrence and carcinogenicity. However, studies on NPAHs in soils, especially in agricultural soils, are still limited. In this study, a systematic monitoring campaign of 15 NPAHs and 16 polycyclic aromatic hydrocarbons (PAHs) was performed in agricultural soils from the Taige Canal basin in 2018, which is a typical agricultural activity area of the Yangtze River Delta. The total concentration of NPAHs and PAHs ranged from 14.4 to 85.5 ng g-1 and 118-1108 ng g-1, respectively. Among the target analytes, 1,8-dinitropyrene and fluoranthene were the most predominant congeners accounting for 35.0% of ∑15NPAHs and 17.2% of ∑16PAHs, respectively. Four-ring NPAHs and PAHs were predominant, followed by three-ring NPAHs and PAHs. NPAHs and PAHs had a similar spatial distribution pattern with high concentrations in the northeastern Taige Canal basin. The soil mass inventory of ∑16PAHs and ∑15NPAHs was evaluated to be 31.7 and 2.55 metric tons, respectively. Total organic carbon had a significant impact on the distribution of PAHs in soils. The correlation between PAH congeners in agricultural soils was higher than that between NPAH congeners. Based on diagnostic ratios and principal component analysis-multiple linear regression model, vehicle exhaust emission, coal combustion, and biomass combustion were the predominant sources of these NPAHs and PAHs. According to the lifetime incremental carcinogenic risk model, the health risk posed by NPAHs and PAHs in agricultural soils of the Taige Canal basin was virtually negligible. The total health risk in soils of the Taige Canal basin to adults was slightly higher than that to children.

Sedimentary spatial variation, source identification and ecological risk assessment of parent, nitrated and oxygenated polycyclic aromatic hydrocarbons in a large shallow lake in China.

Because polycyclic aromatic compounds (PACs) are persistent, universal, and toxic pollutants, understanding the potential source and ecological risk thereof in lakes is critical to the safety of the aquatic environment. Here, a total of 25 sedimentary samples were collected from Lake Taihu, China, in 2018. The total concentrations of 16 parent polycyclic aromatic hydrocarbons (PAHs), 15 nitrated PAHs (NPAHs), nine oxygenated PAHs (OPAHs), and five hydroxy-PAHs (OH-PAHs) ranged from 294 to 1243, 3.0 to 54.5, 188 to 1897, and 8.3 to 51.7 ng/g dw, with the most abundant compounds being fluoranthene, 1,8-dinitropyrene, 6H-Benzo[cd]pyren-6-one, and 2-phenylphenol, respectively. The spatial distribution of PACs in sediments of Lake Taihu showed elevated concentrations from east to west due to economic development and transportation. The positive correlations between most paired PAHs indicate that these compounds likely originated from similar sources. The total organic carbon and organic matter contents affected the distribution characteristics of PACs in sediments. Diagnostic ratios, principal component analysis-multiple linear regression (PCA-MLR), and positive matrix factorization (PMF) were integrated to identify the sources. PACs had various sources including combustion, petroleum leakage, traffic emissions, hydroxyl metabolism, and other oxidation pathways in sediments of Lake Taihu. The PMF (R2 > 0.9824), which showed better optimal performance compared with PCA-MLR (R2 > 0.9564) for PAHs and derivatives, is recommended as the preferred model for quantitative source analysis. Ecological risk assessment showed that the risk quotient values of OPAHs in sediments were much higher than those of other PACs and should be given special attention.

Occurrence and risk of iodinated X-ray contrast media in source and tap water from Jiangsu province, China.

Microcontaminants in the water environment have received increasing attention due to their adverse effects on human health and wildlife. However, iodinated X-ray contrast media (ICM), a type of microcontaminants, have not yet been systematically documented in source and tap water. This study investigated ICM in water samples via a sampling activity from 25 drinking water sources and their corresponding 30 household taps in south-central Jiangsu Province, China. The total concentrations of ICM ranged from 14.2 to 138.5 ng/L in source water and 3.7 to 101.3 ng/L in tap water, respectively. The calculated average water treatment efficiency to remove ICM is 38.3% with large variation under different processes (ranging from 7.3% to 75.7%), which implied that ICM could not be effectively removed using current treatment technologies. By integrating other ICM into the predominant compound iohexol with relative potency factors, the health risks of total ICM through water consumption were assessed using the Monte Carlo simulation. The results concluded that the risk of ingesting ICM through tap water was not a major health concern for adults, teens, or children in the study area. Nevertheless, due to the lack of long-term toxicity data relevant for humans for ICM, this risk may be underestimated, which requires further research.

Safety assessment of marigold flavonoids from marigold inflorescence residue.

ETHNOPHARMACOLOGICAL RELEVANCE: Marigold flavonoids, extracted from marigold (Tagetes erecta L.) inflorescence residues, have attracted significant attention with respect to antioxidant, anti-inflammatory and chelating properties. However, the toxicity of marigold flavonoids have not yet been fully investigated. AIM OF THE STUDY: The main purpose of this study was to assess the safety of marigold flavonoids extracted from Marigold (Tagetes erecta L.) in order to provide information on its nonclinical safety. Thus, the acute oral toxicity, in vitro Ames test, sperm aberration study, bone marrow micronucleus test, subchronic oral toxicity test, and teratogenic potential were carried out in rats or mice. MATERIALS AND METHODS: For an acute oral toxicity test, SD rats and ICR mice (male and female, n = 5) orally received a single dose of 5000 mg/kg marigold flavonoids. Evaluation of marigold flavonoids genotoxic potential with a battery of tests, including an in vitro bacterial reverse mutation test using four mutant strains of Salmonella typhimurium (TA97、TA98、TA100、TA102), an sperm aberration test and an in vivo micronucleus test using bone marrow cells ICR mice that were orally administered marigold flavonoids, an subchronic oral toxicity study and teratogenic test employing male and female SD rats that were orally administered marigold flavonoids. All animals tests were completed in accordance with GB 15193 for toxicity tests. RESULTS: In the acute oral toxicity test, marigold flavonoids given at the dose of 5000 mg/kg body weight for 14 days didn't produce any abnormal clinical symptoms or mortality in SD rats and ICR mice (both sex, n = 5). There was no evidence of genotoxicity of marigold flavonoids based on the results of the in vitro bacterial reverse mutation test (up to 1250 µg/plate), the sperm aberration test (up to 5000 mg/kg body weight), the in vivo micronucleus test (up to 5000 mg/kg body weight), the subchronic oral toxicity study (up to 10 g/kg feed dose) and the teratogenic test (up to 1250 mg/kg body weight). CONCLUSIONS: We found that marigold flavonoids are safe with regard to acute toxicity in rats or mice as well as genotoxicity such as mutagenesis or clastogenesis under the present experimental conditions. These results might support the safety of marigold flavonoids as a potential therapeutic material for the traditional use of herbal medicines and for the further development of novel antioxidant.

Functional Ultra-High Molecular Weight Polyethylene Composites for Ligament Reconstructions and Their Targeted Applications in the Restoration of the Anterior Cruciate Ligament.

The selection of biomaterials as biomedical implants is a significant challenge. Ultra-high molecular weight polyethylene (UHMWPE) and composites of such kind have been extensively used in medical implants, notably in the bearings of the hip, knee, and other joint prostheses, owing to its biocompatibility and high wear resistance. For the Anterior Cruciate Ligament (ACL) graft, synthetic UHMWPE is an ideal candidate due to its biocompatibility and extremely high tensile strength. However, significant problems are observed in UHMWPE based implants, such as wear debris and oxidative degradation. To resolve the issue of wear and to enhance the life of UHMWPE as an implant, in recent years, this field has witnessed numerous innovative methodologies such as biofunctionalization or high temperature melting of UHMWPE to enhance its toughness and strength. The surface functionalization/modification/treatment of UHMWPE is very challenging as it requires optimizing many variables, such as surface tension and wettability, active functional groups on the surface, irradiation, and protein immobilization to successfully improve the mechanical properties of UHMWPE and reduce or eliminate the wear or osteolysis of the UHMWPE implant. Despite these difficulties, several surface roughening, functionalization, and irradiation processing technologies have been developed and applied in the recent past. The basic research and direct industrial applications of such material improvement technology are very significant, as evidenced by the significant number of published papers and patents. However, the available literature on research methodology and techniques related to material property enhancement and protection from wear of UHMWPE is disseminated, and there is a lack of a comprehensive source for the research community to access information on the subject matter. Here we provide an overview of recent developments and core challenges in the surface modification/functionalization/irradiation of UHMWPE and apply these findings to the case study of UHMWPE for ACL repair.

Surface Functionalization of Electrodes and Synthesis of Dual-Phase Solid Electrolytes for Structural Supercapacitors.

The interface between structural electrodes and solid electrolytes plays a key role in the electrical-mechanical properties of energy storage structures. Herein, we present a surface functionalization method to improve the ion conduction efficiency at the interface between a structural electrode and a solid electrolyte that consists of a bi-continuous network of epoxy and ionic liquid (IL). Composite supercapacitors made with this electrolyte and carbon fiber (CF) electrodes coated with manganese dioxide (MnO2) demonstrate that treating the electrodes with the silane can increase the areal capacitance by 300% without degrading the tensile strength. The dual-phase electrolyte containing 40 wt % IL and 60 wt % epoxy exhibits the highest multifunctional performance, measured by the product of stiffness and ionic conductivity. The outstanding mechanical and energy storage properties demonstrate that the silane treatment of MnO2-coated CF fabric structural electrodes is a promising method for future high-performance structural composite supercapacitors.

Removal kinetics and mechanisms of tetrabromobisphenol A (TBBPA) by HA-n-FeS colloids in the absence and presence of oxygen.

The colloid of ferrous sulfide modified by humic acid (HA-n-FeS) shows good reduction and immobilization efficiency for variable-valence heavy metals in wastewater. The removal efficiency of HA-n-FeS for halogenated organic pollutants, however, remains unclear, especially in the absence and presence of oxygen. This study addressed this issue by exploring the effect and mechanism of dissolved oxygen on the degradation of tetrabromobisphenol A (TBBPA) by the HA-n-FeS colloid in water. The results showed that the removal efficiency of different concentrations of TBBPA (5,10, and 20 µm) by the HA-n-FeS colloid was 33.16%, 20.48%, and 22.37% in the absence of oxygen, respectively. When TBBPA reacted with the HA-n-FeS colloid, the concentration of Fe(II) and S(-II) remained stable. The adsorption of HA-n-FeS was the main mechanism of removing TBBPA in the absence of oxygen. In the presence of oxygen, the removal efficiency of TBBPA by the HA-n-FeS colloid was 82.37%, 56.80%, and 43.78% (for the above-mentioned TBBPA concentrations), respectively. In addition, the removal capacity of TBBPA by HA-n-FeS was 39.63, 52.21, and 89.75 mg/g, respectively. The concentration of Fe(II) and S(-II) decreased rapidly in time. Among them, the HA-n-FeS colloid removed part of the TBBPA through chemical adsorption. The main way of chemical adsorption was pore adsorption and functional group (olefin CC, phenolic hydroxyl group O-H, alcohol group C-O) combination. Besides, the HA-n-FeS colloid degraded part of the TBBPA into BPA through reduction, in which 17.72% of TBBPA was removed by the reduction of HA-n-FeS colloid. Fe(II) was the main contributor to the reductive degradation of TBBPA. Furthermore, active species (1O2 and •O2-) played a minor role in the removal of TBBPA by the HA-n-FeS colloids with oxygen, where 13% of TBBPA was removed by 1O2 and •O2-. Therefore, in practical applications, the aeration method can be used to significantly improve the removal efficiency of TBBPA by HA-n-FeS colloids in water.

A comparative study on adsorption behavior of iodinated X-ray contrast media iohexol and amidotrizoic acid by magnetic-activated carbon.

As persistent and ubiquitous contaminants in water, iodinated X-ray contrast media (ICM) pose a non-negligible risk to the environment and human health. In this study, we investigated the adsorption behavior of two typical ICM compounds, iohexol (IOH) and amidotrizoic acid (DTZ), on magnetic activated carbon. Theoretical investigations, using density functional theory, identified the molecule structures and calculated the molecular diameters of IOH (1.68 nm) and DTZ (1.16 nm), which revealed that ICM could be adsorbed by mesopores and larger micropores. Therefore, magnetic activated carbon with a porous structure was prepared by the co-precipitation method to investigate the adsorption mechanism of IOH and DTZ. MAC--5 (magnetic activated carbon with a theoretical iron oxide content of 37%) showed the best adsorption ability for both IOH and DTZ, with maximum adsorption capacities of 86.05 and 43.00 mg g-1, respectively. Adsorption kinetics and isotherm models were applied to explore the mechanisms involved, and the effects of solution pH, initial concentration, temperature, ionic strength, and natural organic matter were also investigated. The pore filling effect, π-π stacking, hydrogen bonding, and electrostatic interaction, were found to be the main adsorption mechanisms. The co-adsorption data showed that competition may occur in ICM coexisting environments. Interestingly, the used MAC--5 could be successfully regenerated and its adsorption efficiency did not decrease significantly after five cycles, indicating that it is a promising adsorbent for ICM. The results from this study provide some new insights for the treatment of water containing ICM.

Evaluating the adsorption performance of Tenax TA® in different containers: An isolation tool to study the bioaccessibility of nitro-PAHs in spiked soil.

The improved in vitro gastrointestinal simulation methods, with the addition of the adsorption sink, are considered as a promising tool for predicting the bioaccessibility of contaminants. However, the problem associated with the recovery of the adsorption sink from the complex matrix needs more understand. Although previous studies tried to solve this shortcoming by using the containers (a vessel to hold the adsorption sink), there is no systematic comparison study on the impact of containers on bioaccessibility till now, especially for nitro-polycyclic aromatic hydrocarbons (nitro-PAHs). In order to understand the problem, commonly used containers in previous studies (dialysis bags and stainless-steel screen) were selected and deployed in the Fed Organic Estimation Human Simulation Test (FOREhST) method to compare the effects of these containers on the bioaccessibility of nitro-PAHs desorbed from the five different types of soils into the gastrointestinal fluid (GIF). Results showed that in order to maintain a constant sorptive gradient for the high molecular weight (MW) nitro-PAHs, 0.25 g of Tenax TA® were required in FOREhST. Compared with Tenax TA® encapsulated in dialysis bag (Tenax-EDBG), the use of Tenax TA® encapsulated in dissolution basket (Tenax-EDBT) significantly increased the bioaccessibility of nitro-PAHs in the soil from 5.6-31.4% to 17.2-70.6%, due to the better diffusion performance. The bioaccessibility of nitro-PAHs by FOREhST extraction with Tenax-EDBT showed a significant negative correlation with soil total organic carbon (TOC), whereas a weak correlation with pH. This study provides the researchers with a more standardized in vitro method to quantify the bioaccessibility of PAHs and their derivatives in soil.

Targeting epigenetically maladapted vascular niche alleviates liver fibrosis in nonalcoholic steatohepatitis.

Chronic hepatic diseases such as nonalcoholic steatohepatitis (NASH) suppress liver regeneration and lead to fibrosis and cirrhosis. Decoding the cellular and molecular network underlying this fibrotic maladaptation might aid in combatting NASH, a growing health challenge with no approved therapies. Here, we used multiomics analysis of human cirrhotic liver, a Western diet­ and carbon tetrachloride (CCl4)­induced minipig NASH model, and genetically modified mice to unravel the landscape of the vascular adaptome at the single-cell level, in which endothelial cells (ECs) and TH17 cells jointly contribute to liver cirrhosis. We found that epigenetics-dependent hepatic vascular maladaptation enriches fibrogenic TH17 cells to promote liver fibrosis in mice, minipigs, and human patients with cirrhosis. Further analysis of humans, minipigs, and mice suggested that cross-talk between histone deacetylase 2 (HDAC2) and DNA methyltransferase 1 (DNMT1) promoted liver EC maladaptation to promote production of angiocrine IGFBP7 and ADAMTS1 in extracellular vesicles, recruiting fibrogenic TH17 cells to the liver. Pharmacological targeting of HDAC2 and DNMT1 alleviated fibrosis in a minipig NASH model. We conclude that epigenetically reprogrammed vascular adaptation contributes to liver fibrosis. Targeting of a vascular adaptation node might block maladaptive vascularization to promote liver regeneration in NASH.

Copper(II)-Catalyzed Tandem Reaction: Synthesis of Furo[3,2-c]coumarin Derivatives and Evaluation for Photophysical Properties.

An efficient protocol for synthesizing furo[3,2-c]coumarin derivatives is described. The novel reaction could afford the desired furocoumarins with good to excellent yields in a mild and rapid manner. Large substrate scope screening and scale-up preparation have also been accomplished, and selected compounds were evaluated for their photophysical properties.

The inhibitory effect of in situ extracellular polymeric substances on trimethoprim adsorption by activated sludge.

The extracellular polymeric substances (EPS) of activated sludge are a mixture of high molecular weight polymers secreted by microorganisms, which are mainly composed of proteins, polysaccharides and humic substances. It is widely accepted that EPS have a good adsorption ability for pollutants with different functional groups. However, recent studies showed the EPS had an inhibitory effect on pollutant sorption, which is contradictory to previous viewpoint. Therefore, in this study, three types of activated sludge with different EPS contents and compositions were used to investigate the role of EPS in an antibiotic-trimethoprim (TMP) sorption process at environmentally relevant concentration. The in situ experiments results showed the adsorption capacity of activated sludge for TMP were increased from 2.98, 5.37 and 28.33 µg/g VSS to 7.87, 12.93 and 150.24 µg/g VSS in nitrifying activated sludge, wastewater treatment plant activated sludge and anaerobic ammonia-oxidized activated sludge, respectively after EPS extracted. The adsorption process can be well described by the pseudo-second-order kinetic model. Results of zeta potential, contact angles and infrared spectrum showed TMP replacing proteins embedded into the cell membrane enhancing the TMP adsorption capacity of activated sludge after EPS extraction. Our results demonstrated that less proteins in EPS of activated sludge is more beneficial for TMP adsorption removal.

Combined effects of polyethylene and organic contaminant on zebrafish (Danio rerio): Accumulation of 9-Nitroanthracene, biomarkers and intestinal microbiota.

Microplastics, as emerging pollutant, are predicted to act as carriers for organic pollutants, but the carrier role and bio-toxic effects with other pollutants in environments are poorly acknowledged. In this study, both the single and combined effects of polyethylene (PE, 10 and 40 mg/L) with the particle size of 100-150 µm and 9-Nitroanthracene (9-NAnt, 5 and 500 µg/L) on zebrafish (Danio rerio) had been investigated. The results illustrated that PE could be as 9-NAnt carrier to enter into zebrafish body, but significantly reduced the bioaccumulation of 9-NAnt, due to the occurrence of adsorption interactions between the simultaneous presence of both PE and 9-NAnt. After 4 days, the enzymes activity of cytochrome P4501A, acetylcholinesterase (AChE), superoxide dismutase (SOD), catalase (CAT), lactate dehydrogenase (LDH), and the abundance of malondialdehyde (MDA), lipid peroxide (LPO) responded strongly to low-dose PE exposure (10 mg/L). After 7 days exposure to PE-9-NAnt (40 mg/L), the P4501A activity increased significantly, but the activities of AChE and LDH were inhibited clearly, causing certain neurotoxicity and disorders of energy metabolism to zebrafish. The analysis of integrated biomarker response index (IBR) suggested that PE had greater bio-toxicity to zebrafish in all exposure groups after short-term exposure, but the PE-9-NAnt complex showed greater bio-toxicity after 7 days, which indicated that complex exposure of PE-9-NAnt had a delayed effect on the bio-toxicity of zebrafish. Furthermore, analysis of the intestinal microbiota exhibited that under the conditions of the exposure group with 9-NAnt, the relative abundance of the five dominant bacterial phyla (Proteobacteria, Firmicutes, Fusobacteriota, Bacteroidota and Verrucomicrobiota) changed greatly. Overall, this study confirmed that PE could carry 9-NAnt into fish causing bioaccumulation, but in the case of coexisting exposures, PE reduced 9-NAnt bioaccumulation, suggesting that microplastics with other emerging pollutants in chronic toxicity are probably next objects in future works.